This project is aimed at investigation of mechanisms of pathogenesis of murine leukemia viruses. The Friend murine leukemia helper virus (F-MuLV) induces early hemolytic anemia (EHA) three weeks post inoculation of newborn mice. In contrast, Moloney murine leukemia virus (M-MuLV) does not induce severe EHA. In order to define which portions of the F-MuLV and M-MuLV genomes were responsible for the differences in induction of EHA, recombinant retroviruses were constructed exchanging different portions of the genomes of F-MuLV and M-MuLV. The results indicated that only retroviruses containing the U5-gag-pol region of F-MuLV could induce EHA. The precise sequence in this region responsible for the pathogenesis of EHA is now being defined by construction of additional recombinant retroviruses and sitespecific mutagenesis.